Abstract

A study was made of the influence of ethanol on the kinetics of valproic acid (VPA) in rats that received single doses of both compounds. Three groups of animals received a single dose of VPA (100 mg/kg) through a gastric tube, alone (Group I: controls) or together with ethanol at doses of 2.5 mg/kg (Group IIa) and 5 mg/kg (Group IIb). VPA was determined using the homogeneous immunoassay EMIT. VPA kinetics were fitted to an open two-compartment model with a first order two phase absorption process defined by the constants Ka1 and Ka2, where Ka1 would reflect the rate of gastric emptying, and Ka2 could express the true absorption constant. The groups of animals receiving ethanol showed a statistically significant decrease (p less than 0.05) in plasma concentrations of VPA compared with the control group. Ka2 increased in groups IIa and IIb compared with the control group (35.79 hr-1 and 36.61 hr-1 vs. 28.18 hr-1). However, Ka1 decreased in group IIb as compared with the control rats (2.34 hr-1 vs. 4.18 hr-1), whereas no modifications were seen in group IIa (4.35 hr-1). The t1/2 beta was greater in groups IIa and IIb than in the controls (8.77 hr and 7.78 hr vs. 4.55 hr), and Ke was lower in those groups than in the controls (0.86 hr-1 and 0.48 hr-1 vs. 0.98 hr-1), suggesting a decrease in the elimination of VPA following administration of a single dose of ethanol.